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妇科癌症中的免疫检查点抑制剂:文献更新与临床研究展望

Immune Checkpoint Inhibitors in Gynecological Cancers: Update of Literature and Perspectives of Clinical Research.

作者信息

Gadducci Angiolo, Guerrieri Maria Elena

机构信息

Department of Experimental and Clinical Medicine, Division of Gynecology and Obstetrics University of Pisa, Pisa, Italy

Department of Experimental and Clinical Medicine, Division of Gynecology and Obstetrics University of Pisa, Pisa, Italy.

出版信息

Anticancer Res. 2017 Nov;37(11):5955-5965. doi: 10.21873/anticanres.12042.

Abstract

The presence of tumor infiltrating lymphocytes (TILs) influences the clinical outcome of cancer patients and immune checkpoint inhibitors (ICPI) have been approved for treating different types of malignancies. In this review, we assess the scanty data from literature and the perspectives of clinical research about the use of ICPI in gynecological cancers. These agents have obtained objective response rates ranging from 5.9% to 15% in early phase Ib-II trials, including patients with platinum-resistant ovarian cancer, whereas only anecdotal data are available for patients with recurrent, heavily pretreated endometrial cancer. Several ongoing trials are investigating ICPI alone or in combination with chemotherapy or with other biological agents in untreated and recurrent ovarian cancer, advanced and recurrent endometrial cancer, as well as advanced and recurrent cervical cancer. Breast cancer (BRCA)-mutated high-grade serous ovarian cancers, clear cell ovarian cancers with microsatellite instability (MSI), POLE ultramutated and MSI hypermutated endometrial cancers are likely to be sensitive to programmed cell death (PD-1)/PD-ligand 1 (PD-L1) pathway blockade, since these tumors show increased neoantigen load, increased CD8 TIL number and PD-1 and PD-L1 overexpression. ICPI could have a role as maintenance treatment in patients with persistent, recurrent or metastatic cervical cancer in response after chemotherapy.

摘要

肿瘤浸润淋巴细胞(TILs)的存在会影响癌症患者的临床结局,免疫检查点抑制剂(ICPI)已被批准用于治疗不同类型的恶性肿瘤。在本综述中,我们评估了文献中的少量数据以及关于ICPI在妇科癌症中应用的临床研究观点。在早期Ib-II期试验中,这些药物在包括铂耐药卵巢癌患者在内的人群中获得了5.9%至15%的客观缓解率,而对于复发、经过大量预处理的子宫内膜癌患者,仅有个案数据。几项正在进行的试验正在研究ICPI单独或与化疗或其他生物制剂联合用于未治疗和复发的卵巢癌、晚期和复发的子宫内膜癌以及晚期和复发的宫颈癌。乳腺癌(BRCA)突变的高级别浆液性卵巢癌、具有微卫星不稳定性(MSI)的透明细胞卵巢癌、POLE超突变和MSI高突变的子宫内膜癌可能对程序性细胞死亡(PD-1)/PD配体1(PD-L1)通路阻断敏感,因为这些肿瘤显示出新抗原负荷增加、CD8 TIL数量增加以及PD-1和PD-L1过表达。ICPI可作为化疗后缓解的持续性、复发性或转移性宫颈癌患者的维持治疗。

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